The objective of the present research proposal is to determine the chemical nature of the DNA-protein cross-linking formed in mammalian chromatin when it is irradiated with ultraviolet light. In particular we will examine the following questions. Which nucleic acid bases and amino acids are involved in forming the cross-links? What are the chemical structures of those adducts that are important in forming DNA-protein cross-links? The experiments planned will emphasize the nature of the cross-links formed between DNA and the histone fractions H2A, H2B, H3, and H4 when mammalian chromatin is irradiated, both in vitro and in cultured mammalian cells.